Clinical Research Directory

Personalized Ultrasonic Brain Stimulation for Depression (R61)

This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ultrasound stimulation will be delivered using a range of stimulation parameters during psychological and physiological monitoring. Individualized optimal targets will be selected using structural MRI and diffusion tractography. Brain target engagement will be evaluated using functional MRI.

Feasibility and Acceptability of an E-learning Dialectical Behavior Therapy Skills Course

Dialectical behavior therapy (DBT) is a comprehensive, third-wave psychological intervention designed for patients with complex and severe behavioral, emotional, and interpersonal dysfunction. DBT has since been adapted to shorter, briefer, "skills training" formats, which have been effective for a number of mild-to-moderate mental health conditions, including depression and anxiety. Moreover, internet-delivered formats of DBT (iDBT) have similarly started to build support for their effectiveness, although there are fewer studies on digital formats. One study found that over 12 weeks, iDBT was deemed acceptable (e.g., 50% of participants were still active after 4 weeks) and there were improvements in multiple symptom domains, such as depression, anxiety, suicidality, functional disability, as well as alcohol and substance dependence. In the current study, the investigators will examine the feasibility, acceptability, and potential efficacy of a new iDBT intervention, packaged as an online e-learning skills course, with adult participants. The study is a pilot trial as iDBT has never been tested in this format through formal research. Thus, this pilot study aims to examine whether this course is usable, practical, and potentially useful to others in the future. The investigators will recruit up to 40 individuals with mild-to-moderate depression and anxiety for an 8-week study. Following a phone screen to determine eligibility, participants will complete a baseline session where they will provide consent, complete a brief interview and questionnaires, and register for the e-learning skills course. Over the course of 8 weeks, participants will be exposed to material adapted from a DBT manual in a self-guided manner. Participants will complete follow-up assessments at 4 and 8 weeks.

Effectiveness of Internet-based Unified Protocol (iUP) for Emotional Problems: A Randomized Controlled Trial

The goal of this clinical trial is to learn if an internet-based Unified Protocol (iUP) intervention is effective for treating depression and anxiety disorders in Hong Kong young adults aged 18-29 years. This study is conducted within the eClinic, a public mental health support service provided by a Hong Kong non-government organisation (NGO). The main questions it aims to answer are: * Is the iUP intervention effective in treating depression and anxiety disorders? * How long is the treatment effect sustained after the intervention ends? * Does the intervention also improve real-world functioning, such as occupational and academic performance? Researchers will compare participants who receive the iUP intervention immediately with those in a wait-list control group (who receive no intervention during the waiting period) to evaluate the effectiveness of iUP. Participants will: * Receive a 14-week iUP intervention either immediately or after a 14-week waiting period according to randomisation * Complete weekly and follow-up questionnaires throughout the study period

Intervention to Reduce HIV Related Stigma Among Pregnant and Postpartum Women

Purpose of this Study: The main purpose of this study is to adapt an existing evidence-based intervention, Project Accept Post-Test Support Services (PTSS) Module 3, specifically for pregnant and postpartum women living with HIV (WLWH) in Ghana. The adapted intervention aims to reduce HIV-related stigma and improve adherence to antiretroviral therapy (ART) and mental health symptoms, such as depression and anxiety, among this vulnerable population. Why was this study done? (Background): HIV-related stigma is a major obstacle for women living with HIV, particularly pregnant women in Sub-Saharan Africa (SSA), hindering their engagement in HIV care and adherence to ART. This contributes to poor health outcomes, including inadequate viral suppression, depression, and an ongoing risk of HIV transmission to their children and sexual partners. While effective HIV stigma-reduction interventions exist for the general adult population living with HIV, there is a critical lack of tailored interventions for pregnant and postpartum WLWH in SSA. This study addresses this gap by adapting a proven intervention (Project Accept PTSS Module 3), which has shown success in reducing stigma and improving outcomes in other populations, for this specific group in Ghana, where HIV-related stigma remains disproportionately high. Who participated in this study? (Target Population): This study will involve several groups: Pregnant and postpartum women living with HIV: 30 women will participate in in-depth interviews to share their experiences with stigma and HIV care. HIV care providers: 20 providers will participate in in-depth interviews to offer their perspectives on stigma and care provision. Stakeholders: This group will include HIV care providers, program administrators/directors, and pregnant and postpartum women. They will collaborate in the iterative process of adapting the intervention. Pregnant women living with HIV (for feasibility testing): 90 pregnant women will be randomized, with half receiving the adapted intervention and half receiving standard care, to assess the intervention's feasibility, acceptability, and preliminary impact. What happened in this study? (Intervention/Methods): This 3-year study has three main aims: Understanding Stigma Experiences: Researchers will describe the experiences of stigma and HIV care from the perspectives of pregnant and postpartum WLWH and compare them with providers' experiences. This will involve longitudinal data collection and in-depth interviews to understand how stigma affects women's health, clinical care (e.g., provider discrimination, ART adherence), and mental health over time. Intervention Adaptation: Project Accept PTSS Module 3 will be adapted specifically for pregnant and postpartum WLWH using the ADAPT-ITT framework. This involves an iterative process with stakeholders to ensure the intervention is culturally and gender-appropriate, enhancing its acceptability for the target population. Feasibility and Preliminary Impact Assessment: The study will assess the feasibility and acceptability of the adapted intervention. Ninety pregnant women will be randomly assigned to either receive the intervention or continue with standard care. Researchers will then estimate the intervention's potential impact on anticipated and internalized HIV-related stigma (primary outcomes), as well as ART adherence and symptoms of anxiety and depression (secondary outcomes). What were the results of this study? (Outcomes): As a preliminary and adaptation study, this research aims to: Provide essential data to inform and justify a larger, fully-powered randomized clinical trial to rigorously evaluate the adapted intervention's effectiveness. Identify potential indicators associated with mother-to-child transmission of HIV. Develop a model that can be applied to other Sub-Saharan African countries facing similar challenges. Foster new collaborations focused on HIV-related stigma among women in Ghana. Build research capacity among researchers in sub-Saharan Africa. What are the side effects of the treatments in this study? (Safety): This study focuses on a behavioral intervention (a support and counseling module) rather than a drug or medical treatment. Therefore, typical physical side effects associated with medications are not expected. The intervention aims to improve well-being and health outcomes by addressing psychosocial factors. Any adverse events or discomfort experienced by participants will be carefully monitored and addressed in accordance with ethical guidelines. What are the conclusions of this study? (Implications/Future Plans): The findings from this study are expected to demonstrate the feasibility and potential impact of a culturally and gender-tailored HIV stigma-reduction intervention for pregnant and postpartum WLWH in Ghana. This research will be foundational for launching a larger-scale clinical trial to definitively test the intervention's efficacy.

A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD. For more information about the EMBRACE study, including participating study locations, and to register your interest in learning more about participation, please visit the study website: https://embrace-mdd-trial.com/

Open-Label Psilocybin Study in Transdiagnostic Population

The primary objective of this study is to investigate the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms. The secondary objective of this study is to determine whether individuals with functional impairments due to psychiatric symptoms will experience statistically significant symptom reduction and functional improvement from baseline symptom measurements (Visit 3) to 1-week (Visit 7), 4-weeks (Visit 8), and 6-weeks (Visit 9) post dosing. The investigators will recruit individuals with mood, anxiety, trauma, addictive, or related symptomatology, and who have functional impairment associated with these symptoms. A DSM-5 diagnosis is not required (nor is it an exclusion). The investigators will allow for comorbidity and only exclude based on psychological and physiological safety considerations. Critically, this approach will allow us to assess the tolerability of our interventions in individuals who would typically be excluded from efficacy studies due to various comorbid DSM-5 conditions. The investigators will employ an open-label study where participants will be given one dose of oral psilocybin 25mg. The investigators will also have follow-up visits at 1, 4, and 6 weeks and an optional long-term follow-up at 3, 6, and 12 months.

Digital Intervention for Physical Activity

The present study will assess the effects of a four-week digitally delivered intervention on physical activity and depressive symptoms among adults experiencing at least moderate depressive symptoms. The main questions this research aims to answer are: * Does a digitally-delivered intervention increase physical activity levels? * Does a digitally-delivered intervention reduce symptoms of depression? Researchers will compare an intervention promoting physical activity to a passive control (does not receive the intervention) group to see if the intervention reduces depressive symptoms and increases physical activity levels. Participants will: * Visit the laboratory at two separate time points before group assignment, separated by one week of physical activity monitoring * Be randomly assigned to complete four weeks of a digital intervention prompting engagement in physical activity or have their mental health symptoms monitored over four weeks (i.e., passive control group) * Visit the laboratory at two separate time points after the intervention, separated by one week of physical activity monitoring

Microbiota Modulation for Psychiatry Patients

The investigators aim to confirm pilot study findings (REB 119638) on the effects of delayed release apple cider vinegar (drACV). The investigators aimed to determine the feasibility that the acetate in ACV would counteract the problematic weight gain and metabolic side effects associated with the most common psychiatric medications. Our pilot study recruited 11 participants from the First Episode Mood and Anxiety Program (FEMAP) who had experienced (by self-report) weight gain concurrent with medication use. The investigators found that drACV was well tolerated with adherence above 90% and resulted in reduced LDL cholesterol, improved lipids in 7 participants, altered microbiota composition in the direction associated with improved metabolic and mental health outcomes, and the emergence of a potential "responder phenotype". The investigators did not, however, find significant effects on weight. The investigators aim to expand that study by 1) including a larger sample; 2) Conducting a detailed analysis of the microbiome and identifying immune and genomic factors associated with response, thereby further defining responder and non-responder phenotypes that emerged in the initial analysis, 3) collecting additional biological, psychological, and social data to permit complex multivariate modelling on gene-environment interactions for mechanistic research. The investigators will seek to recruit sixty-two participants from FEMAP, the General Adult Ambulatory Mental Health Services (GAAMHS) and Child and Adolescent Mental Health Services at LHSC. Participants need to have experienced weight gain by self-report and clinician estimation, be psychiatrically stable on steady doses of medication, and be between the ages of 16-45.

Understanding the Neural Underpinnings of Risk-Taking Behavior in Psychiatric Disease

The purpose of this study is to understand how the orbitofrontal cortex (OFC), a region at the front of the brain, guides decisions about whether to pursue a possible reward when doing so also carries a risk of loss, and how this process is altered in depression. People with depression are often less motivated by rewards and more sensitive to potential losses, leading them to avoid situations that others would approach. The OFC is thought to play a central role in these "approach or avoid" decisions, but how it normally does so, and what goes wrong in depression, is not well understood. This study asks two questions: (1) How does activity in different parts of the OFC signal the decision to approach or avoid? (2) Does this activity differ in people with depression in a way that explains a bias toward avoidance? We hypothesize that the medial OFC (toward the middle of the brain) signals approach, the lateral OFC (toward the side of the brain) signals avoidance, and that in depression the medial OFC signal is weakened, tipping decisions toward avoidance. Participants are adults who are hospitalized with stereo-EEG (sEEG) electrodes already placed in the brain by their medical team, either to locate the source of seizures in epilepsy or as part of a separate clinical trial for treatment-resistant depression. The electrodes are placed for clinical reasons only, not for this study. During their hospital stay, participants complete a short, game-like computer task (about 20 minutes per session) in which they repeatedly choose whether to approach or avoid options that offer different chances of reward and loss. Their choices and reaction times are recorded along with brain activity from the existing electrodes, and participants rate their mood before each session. The researchers will compare OFC activity during approach versus avoid decisions, use mathematical models of decision-making to measure how strongly each participant weighs rewards and losses, and compare participants with and without depression. No drugs, devices, or brain stimulation are given as part of this study. The findings are intended to guide the development of more targeted brain-stimulation treatments for treatment-resistant depression.

Effect of Neurofeedback and TMS

The goal of this clinical trial is to is to learn whether adding EEG neurofeedback (NFB) to repetitive transcranial magnetic stimulation (rTMS) is safe and feasible for adults with major depressive disorder (MDD). The study will also explore whether combining NFB with TMS may improve depression symptoms and change brain activity related to mood, focus, and rumination. The main questions it aims to answer are: * Is alpha-down neurofeedback safe, tolerable, and feasible for people with MDD? * Does alpha-down neurofeedback improve symptoms of depression, anxiety, and difficulties with attention, emotion regulation, and rumination? * Does combining neurofeedback with TMS produce greater changes in symptoms than either treatment alone? Researchers will compare 3 groups (TMS only, neurofeedback only, and TMS combined with neurofeedback) to see if combining neurofeedback with TMS will produce greater changes in symptoms than either treatment alone. Participants will: * Complete assessments of depression severity, anxiety, and cognitive function. * Complete 5 treatment sessions Monday through Friday. * Receive alpha-down neurofeedback, TMS, or both, depending on their group assignment. * Complete EEG recordings of brain activity before and after treatment. * Complete a questionnaire about their experience in the study.

Theta Burst Stimulation for Refractory Depression in Autism Spectrum Disorder

Evaluate the efficacy of accelerated theta burst stimulation (aTBS) in reducing depressive symptoms in autism spectrum disorder (ASD)

Enhancing Operational Readiness With Digital Self-Managed Cognitive Behavioral Therapy for Insomnia (CBTI)

The goal of this pilot clinical trial is to evaluate the effectiveness and delivery method of a CBTI self-managed digital mobile application in service members. The main questions it aims to answer are: RQ1. Will the delivery of CBTI via a self-managed mobile application over five weeks improve sleep outcomes for service members? RQ2. Will the delivery of CBTI via a self-managed mobile application over five weeks improve secondary outcomes (sleep-related impairment, depression, PTSD symptoms, and quality of life) for service members?

Testing a Non-Deceptive Placebo Intervention for Subclinical Depressive Symptoms

Subclinical depression - depressive symptoms that fall below the threshold for major depressive disorder - is common in young adults and predicts later depressive episodes, yet it often goes untreated. This study tests whether a brief, remotely delivered non-deceptive (open-label) placebo intervention reduces subclinical depressive symptoms over approximately two weeks. Participants aged 18-30 living in Ohio, with PHQ-8 scores in the 5-9 range, are randomly assigned to one of three groups: a non-deceptive placebo group, a blinded control group, or an unblinded control group. All participants complete three remote sessions over 16-18 days and complete the same assessments on the same schedule. Participants in the non-deceptive placebo group additionally receive psychoeducation about placebo effects and placebo pills that are explicitly described as containing no active ingredients, which they take twice daily for two weeks. Participants in the unblinded control group are told they have been assigned to a control condition. Participants in the blinded control group are not told their group assignment until debriefing at the end of the study. The study has two aims. The first is to estimate the effect of the non-deceptive placebo intervention on depressive symptoms and related outcomes. The second is methodological: to determine whether telling control participants that they are in a control group changes their outcomes, and therefore whether the choice of control condition systematically biases estimates of non-deceptive placebo effects.

Accelerated vs. Conventional Theta Burst Stimulation for Late-life Depression

The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.

Mindfulness-based Psilocybin Therapy for PTSD

The goal of this study is to learn how psilocybin delivered with mindfulness-based therapy may help symptoms of posttraumatic stress disorder (PTSD). This is an assessor-blinded, randomized, controlled study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and multimodal MRI measures after administration of one oral dose of psilocybin, accompanied either with standard "psychological support" only; or with standard support plus Mindfulness-based Cognitive Therapy (MBCT).

Dual Neuromodulation for Depression: Boosting TMS With tES

Major depressive disorder (MDD) is a common and disabling condition. Transcranial magnetic stimulation (TMS) is an established non-invasive neuromodulation treatment for depression, but clinical response varies considerably between individuals. One possible reason for this variability is that the effects of TMS may depend on the pattern of ongoing brain activity at the time stimulation is delivered. This mechanistic, randomised, single-blind study will investigate whether synchronising TMS with transcranial alternating current stimulation (tACS), a form of weak electrical brain stimulation, can enhance the neurophysiological and cognitive effects of TMS in people experiencing a current moderate major depressive episode. The combined intervention is referred to as synchronised TMS (tsTMS). Up to 60 participants will be recruited and randomised in a 1:1:1 ratio to one of three groups: (1) TMS synchronised to the peak of a theta-frequency tACS waveform, (2) TMS synchronised to the trough of a theta-frequency tACS waveform, or (3) TMS combined with sham tACS. Participants will receive five daily neuromodulation sessions over one week. The primary objective is to estimate variability in change in emotional processing, measured using the Cambridge Cognition Emotional Bias Task, in order to inform the design and sample size calculation of a future clinical trial. The study will also assess participant acceptability and tolerability of the intervention. Secondary objectives include exploring changes in brain oscillatory activity measured using electroencephalography (EEG), cognitive performance, mood and anxiety symptoms, functional outcomes, and digital biomarkers collected from an optional wearable device. This study is designed to investigate mechanisms and feasibility rather than provide a full therapeutic course of TMS. Findings will be used to inform the development of a future definitive clinical trial evaluating whether synchronised neuromodulation can improve outcomes in depression.

The BAARD Study : Evaluating a Computerized Approach to Treatment Selection in Older Adults With Treatment Resistant Depression.

The goal of this clinical trial is to test whether a personalized approach to treatment selection improves symptoms in older adults with treatment-resistant depression. The main questions it aims to answer is: Will using the BAARD predictive models to select medications lead to better depression outcomes, compared to randomly selecting medications? Researchers will use the BAARD predictive models or random assignment to choose one of two medications to add to patients' current treatment. Patients will be asked to take either aripiprazole or bupropion along with their current medication. Participants will: Take Aripiprazole or Bupropion in addition to their current medication for 10 weeks. Complete follow-up assessments every 1-2 weeks for checkups.

Effectiveness of Health Communication on Depression Elderly in Ho Chi Minh City

The goal of this clinical trial is to learn if a community-based health education and communication program helps prevent and reduce depression in older adults living in Ho Chi Minh City. It will also evaluate how the program affects quality of life and caregiver stress. The main questions it aims to answer are: 1. Does the health education program improve knowledge, attitudes, and practice regarding depression among older adults and their primary caregivers? 2. Does the program reduce depression scores (measured by GDS-30) and improve quality of life in older adults compared to standard care? 3. Does the program help lower caregiving burden and stress among primary caregivers? Researchers will compare an intervention group (older adult and caregiver pairs who receive the education program) to a control group (pairs who receive standard community health care). Participants in the intervention group will: * Attend 5 group education sessions (45-60 minutes each) covering early depression detection, sleep hygiene, nutrition, physical activity, stress management, and caregiver support. * Complete questionnaires at the start and end of the program to measure depression symptoms, quality of life, caregiving burden, and health knowledge.

Effects of Concurrent and Consecutive Repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive Bias Modification (CBM)

The goal of this study is to learn whether combining repetitive transcranial magnetic stimulation (rTMS) with a computerized behavioral intervention (imagery cognitive bias modification, CBM-I) reduces negative interpretation bias and mild-to-moderate depressive symptoms. The study will also examine neural changes in the dorsolateral prefrontal cortex (DLPFC) and whether timing of interventions affects outcomes. The main questions it aims to answer are: Does active TMS reduce negative interpretation bias and depressive symptoms more than sham TMS? Is delivering CBM-I concurrently with TMS more effective than delivering it consecutively (separate sessions) at reducing negative bias and depressive symptoms? Do combined rTMS + CBM-I approaches produce greater neural changes and improved cognitive control over self-referential interpretation than controls? Researchers will compare active TMS versus sham TMS, and concurrent versus consecutive delivery of CBM-I, to test effects on negative bias and depressive symptoms. Participants will: Receive either active rTMS or sham TMS targeting the DLPFC Complete imagery CBM-I sessions either concurrently with TMS or in separate (consecutive) sessions Undergo assessments of negative interpretation bias, depressive symptoms, and neural measures before and after the intervention

An Interrupted Time-Series Pilot Trial of LGBTQ-Affirming Cognitive Processing Therapy for Interpersonal and Developmental Trauma

The researchers are testing a single-group cognitive-behavioral intervention for treating traumatic stress related to interpersonal and developmental trauma in LGBTQ adults. This study requires in-person participation weekly at the UAB campus in Birmingham, AL.

ipRGC as a Potential Biomarker for Predicting Transcranial Magnetic Stimulation Treatment Response in Major Depressive Disorder

This research explores the potential of retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs), as biomarkers for predicting response to transcranial magnetic stimulation (TMS) in treatment-resistant depression (TRD). We also aim to assess the impact of TMS treatment on RGCs and ipRGCs in TRD patients, investigating associations with clinical improvements and cognitive status. A clinical trial involving 44 patients with treatment-resistant depression (TRD) will be conducted. All participants will receive rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Data will be collected pre- and post-intervention, as well as at a 2-month follow-up, using multiple outcome measures, including the post-illumination pupil response (PIPR). The project seeks to confirm the effectiveness of TMS and the potential of RGCs/ipRGCs as predictors of treatment response, thereby facilitating the development of personalized treatment strategies for TRD patients undergoing rTMS therapy.

Transcendental Meditation Intervention to Reduce Burnout and Enhance Resilience Among NewYork-Presbyterian Hospital and Weill Cornell Medicine Employees and Residents

The goal of this study is to learn if a meditation intervention called Transcendental Meditation or TM can be used in a small department at Weill Cornell Medicine to help reduce employees' levels of burnout, anxiety, insomnia, and depression as well as to determine the feasibility and acceptability of the meditation practice by Weill Cornell employees. The main question the study aims to answer is whether: • Levels of burnout, anxiety, insomnia, and depression will be decreased, and overall mental well-being will improve over a 3.5-month period before and after TM intervention. Participants will attend 9 sessions total (8 group sessions and 1 individual session) with a certified TM instructor from The David Lynch Foundation Institute for Mental Health and Resilience where they will gain experience in proper TM techniques. Also, participants will conduct 2 of their own TM sessions at home daily during the course of this study.

Evaluating a Personalised Online Program With Human Support for Women With Depression and Its Impact on Mental Health and Biological Changes

This study aims to evaluate the efficacy of a specially developed internet-based Cognitive Behavioural Therapy (CBT) programme with human interaction-referred to as the 3D programme-tailored specifically for women experiencing moderate depressive symptoms. We hypothesise that participation in the intervention will lead to greater improvements in depression severity, compared to receiving only brief psychoeducational videos, when used as an add-on to treatment as usual (TAU) in this population. The 3D programme is a 10-week blended intervention that includes ten weekly online self-guided modules focused on depression and women's health, along with six individual video sessions with a health/clinical psychologist. The modules cover topics such as mood changes across the menstrual cycle, body image, stress, caregiving, and the impact of gender-based experiences on mental health. To explore how biological factors may influence how participants respond to treatment, the study will collect biological samples. These will be analysed to track hormone and metabolic changes, with the goal of identifying biological markers that might predict who benefits most from the intervention. Ultimately, the results of this study aim to improve access to effective and personalised mental health care for women by evaluating whether a structured and personalised online CBT programme can provide meaningful benefits.

Meditative Neurofeedback for Depression

The goal of this study is to test a meditative neurofeedback intervention for depressed mood.